Near-tetraploidy is a rare cytogenetic abnormality observed in acute myeloblastic leukemia (AML). It was recently suggested that near-tetraploid AML may be associated specifically with t(8;21)(q22;q22). We report here a new case of near-tetraploid AML with double t(8;21)(q22;q22) translocations. A 61-year-old woman was admitted to our hospital because of high fever and pancytopenia. Her bone marrow was markedly hypercellular, with 72% giant and bizarre myeloblasts. These myeloblasts were positive for CD7, CD13, CD19, CD33, CD34, and HLA-DR but negative for CD2 and CD56. The patient's disease was diagnosed as the M2 subtype of AML (by French-American-British classification). Chromosome analysis revealed a karyotype of 45,X,-X, t(8;21) (q22;q22)[1]/90,XXX,-X,t(8;21)(q22;q22)x2,-9[7]/46,XX[12]. Fluorescence in situ hybridization (FISH) analysis with an AML1/ ETO probe detected 4 fusion signals on 2 der(8)t(8;21) and 2 der(21)t(8;21) in near-tetraploid cells. Reverse transcription-polymerase chain reaction analysis revealed the presence of the AML1/ETO fusion transcript. These findings suggested that near-tetraploidy may be a secondary genetic change originating from a diploid clone with t(8;21) and that 2 AML1/ETO fusion genes are generated on the der(8)t(8;21) in near-tetraploid clones. Consideration of the other reported cases suggests that the immunophenotypes of near-tetraploid AML with double t(8;21) are heterogenous, but it is possible that t(8;21)-AML with expression of CD2 or CD7 may be associated with a secondary clonal evolution to near-tetraploidy.